Genetic Variant NM_006662.3:c.7000C>A (chr16-30736616-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006662.3(SRCAP):c.7000C>A(p.Gln2334Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SRCAP
NM_006662.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.93

Publications

2 publications found

Variant links:

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP Gene-Disease associations (from GenCC):

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
Floating-Harbor syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

SRCAP links:

ENSG00000282034 (HGNC:):

ENSG00000282034 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23426482).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	NM_006662.3	MANE Select	c.7000C>A	p.Gln2334Lys	missense	Exon 33 of 34	NP_006653.2	Q6ZRS2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.7000C>A	p.Gln2334Lys	missense	Exon 33 of 34	ENSP00000262518.4	Q6ZRS2-1
ENSG00000282034	ENST00000380361.7	TSL:2	n.6469C>A		non_coding_transcript_exon	Exon 28 of 31	ENSP00000369719.3	A0A0C4DFX4
SRCAP	ENST00000411466.7	TSL:3	c.7000C>A	p.Gln2334Lys	missense	Exon 33 of 34	ENSP00000405186.3	C9J4U4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.23

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.3

PhyloP100

6.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.32

Sift

Uncertain

0.027

Sift4G

Benign

0.27

Polyphen

0.95

Vest4

0.34

MutPred

0.33

Gain of ubiquitination at Q2334 (P = 0.0082)

MVP

0.41

MPC

0.59

ClinPred

0.82

GERP RS

4.5

Varity_R

0.29

gMVP

0.56

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over